A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis

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This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in participants with primary progressive multiple sclerosis. Eligible participants will be randomized 2 : 1 to receive either ocrelizumab or placebo. The blinded treatment period will be at least 120 weeks, followed by an Open Label Extension (OLE) treatment for participants in both groups who in the opinion of the investigator could benefit from further or newly initiated ocrelizumab treatment. Unless terminated early, all participants will continue their treatment with open-label ocrelizumab until the last participant who entered the OLE phase reaches 4 years of open-label ocrelizumab treatment.

Participants with primary progressive multiple sclerosis (PPMS) received placebo matched to ocrelizumab at a schedule interval of 24 weeks up to at least 120 weeks.

Drug: Ocrelizumab

Two IV infusions of 300 mg in each treatment cycle of double blind treatment period; two IV infusions of ocrelizumab 300 mg for Cycle 1 and single IV infusion of ocrelizumab 600 mg for subsequent cycles in OLE phase.

Other: Placebo

Two IV infusions of placebo matched to ocrelizumab in each treatment cycle of double blind treatment period.

Placebo Comparator: Ocrelizumab 600 mg

Participants with PPMS received ocrelizumab as two IV infusions of 300 mg separated by 14 days at a scheduled interval of every 24 weeks up to at least 120 weeks.

Drug: Ocrelizumab

Two IV infusions of 300 mg in each treatment cycle of double blind treatment period; two IV infusions of ocrelizumab 300 mg for Cycle 1 and single IV infusion of ocrelizumab 600 mg for subsequent cycles in OLE phase.

Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period [ Time Frame: Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm ]

The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit >=12 weeks (>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of >= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is <=5.5 points (inclusive), or an increase of >=0.5 points, if baseline EDSS is >5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.

Secondary Outcome Measures
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Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period [ Time Frame: Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm ]

The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit >=12 weeks (>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of >= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is <=5.5 points (inclusive), or an increase of >=0.5 points, if baseline EDSS is >5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.

The SF-36v2 is a 36-item, self- reported, generic measure of quality of life that has been widely used in multiple disease areas. It is composed of 8 health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The PCS score was derived based on the SF-36 V2 User's Manual. Scoring for PCS involves (a) recoding item response values, (b) summing recoded response values for all items in a given scale to obtain the scale raw score, (c) transforming scale raw score to a 0−100 score. The PCS score was computed by (a) multiplying each health domain z score by a scale-specific physical factor score coefficient, (b) summing the resulting products, (c) converting the product total to T score. The total score ranges from 0-100, higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

Percentage of Participants With at Least One Adverse Event (AE) [ Time Frame: From the first infusion up to the study clinical cut-off date 24 July 2015 (up to 229 weeks) ]

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Disease duration from onset of MS symptoms less than (<) 15 years if EDSS greater than (>) 5.0; <10 years if EDSS greater than or equal to (>/=) 5.0

Sexually active male and female participants of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks after the last dose

Exclusion Criteria:

History of relapsing remitting MS, secondary progressive, or progressive relapsing MS at screening

Inability to complete an MRI (contraindications for MRI)

Known presence of other neurologic disorders

Known active infection or history of or presence of recurrent or chronic infection

History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)